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Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Tau change is a key for understanding brain aging and Alzheimer disease

Neurofibrilarlly tangles (NFTs), which consists fibrillar aggregate of hyperphosphorylated tau, are commonly seen in aging and Alzheimer’s disease brain. Based on Braak staging of NFTs, NFT first observed in entorhinal cortex. Then, NFTs spread from entorhinal cortex to limbic and neocortex. NFTs formation in entorhinal cortex may be correlating with memory loss in brain aging, because entorhinal cortex is involved in memory formation, and NFTs in limbic and neocortex may cause dementia in AD, because limbic and neocortex serve higher order brain functions. These suggest that regional development of NFTs is correlated with decline of brain functions in aging and AD. Recent reports suggested that the process of NFT formation, but not NFT itself is involved in neuronal dysfunction. Normally tau binds to microtubules and stabilize them. Once tau receives hyperphosphorylation by activating tau kinases, tau dislodge from microtubules, and starts tau-tau interaction in cytoplasm, forming tau oligomers. When tau oligomers possess b-sheet structure, tau oligomer forms insoluble granular tau aggregate. Granular tau aggregate sticks together, and form NFT. From analysis of tau Tg mouse, we found that hyperphosphorylated tau is involved in synapse loss, and granular tau aggregate is involved in neuronal loss. Thus, during NFT formation, different tau aggregation induces synapse loss, and neuronal loss, leading to brain dysfunction in brain aging and AD. A process of tau aggregation was analyzed by ThT fluorescence and AFM observation. Role of different tau aggregates was determined by analysis of tau Tg mouse. Before tau fibril formation, tau formed soluble oligomer, insoluble granular tau aggregate. Soluble phosphorylated and oligomer tau may be involved in synapse loss, and insoluble granular tau aggregates may play a role in neuronal death. Inhibition of phosphorylated tau, and granular tau aggregation is expected to block a progression of AD symptom by preventing synapse loss and neuronal loss.



Connection between each tau aggregates on synapse loss and neuron loss

Akihiko Takashima

Laboratory for Alzheimer’s disease, Brain Science Institute, RIKEN 2-1 Hirosawa, Wako-shi Saitama 350-0198 Japan

Ph: +81(48) 467-9704
Fx: +81(48) 467-5916

Kenneth@brain.riken.jp